PROJECT SUMMARY Diet is a modifiable exposure that can positively or negatively impact health. More than half of adults and one-third of children use dietary supplements that contain nutrients critical to human health. Currently no metric exists to measure overall total nutrient exposures from all sources. Without measuring the contribution of dietary supplements, exposure classification is incomplete both for nutrient inadequacy and nutrient excess. Using a data-driven strategy with the nationally- representative National Health and Nutrition Examination Survey (NHANES), the assembled, highly qualified team proposes to develop the first comprehensive total nutrient index. Indexes and scores are the preferred metric for use in nutrition because the standardized framework they create allows comparison across studies. In fact, the 2015 Dietary Guidelines for Americans Advisory Committee, building on systematic reviews from the USDA Nutrition Evidence Library, concluded that only diets classified by indexes and scores were useful for informing nutrition policy. The synthesis of the data in the report yielded strong and consistent evidence for dietary patterns classified by indexes and scores, and cardiovascular disease and weight status, and moderate evidence for dietary patterns and Type 2 diabetes. However, no index or score is available that accounts for nutrients derived from dietary supplements and medications. In Aim 1, the team will develop a usual intake model that captures habitual intakes from food, beverages, dietary supplements, and medication, mitigiating the measurement error to the extent possible with self-reported dietary intakes. In Aim 2, the team will characterize the patterns of nutrient intake, using data reduction techniques to create the most salient items to include in the index. The patterns will be carefully examined with regard to biomarkers, health behaviors, and measures of bone and body composition, to create a scoring algorithm for the total nutrient index. In Aim 3, the team will test the reliability and the validity of the total nutrient index. The purpose of the total nutrient index is to provide a tool that can be used for research, monitoring, and policy purposes, and the use of the NHANES data to develop the total nutrient index greatly enhances its external validity. Improving measures of dietary exposure will facilitate researchers' abilities to show causal links to health, ultimately enabling successful intervention strategies.